Leptospirosis, caused by spirochetes of the genus Leptospira, is a zoonotic disease transmitted from natural reservoir mammalian hosts to humans. Humans contract leptospirosis through domestic, occupational and recreational activities, which bring them into contact with fresh surface water or wet soil contaminated by the urine of chronically infected mammalian reservoir hosts. It is precisely the ecological relationship between humans and reservoir hosts that leads to leptospirosis in humans. The major hypothesis underlying this project is that the transmission of leptospirosis to humans is substantially increased by both short and long- term anthropogenic influences on the environment. Two specific hypotheses will be tested: 1) Deforestation with resulting changes in land use (land cultivation, fish farming) that bring humans into closer contact with local mammalian fauna and increases in the amounts of surface waters, soil wetness, and changes in soil pH due to short-term weather fluctuations, will lead to an increase in human leptospirosis cases; and 2) Mammalian faunal populations will change due to deforestation and fluctuations in surface waters, including flooding, that will alter the dynamics of leptospirosis transmission. To address these hypotheses, three specific aims will be pursued: 1) Determine the incidence of acute leptospirosis in humans living in diverse biotopes in and near Iquitos, Peru, identify potential places where people are infected, and identify infecting leptospiral isolates to the serovar and molecular levels; 2) Determine the prevalence of leptospiral infection in potential mammalian reservoir hosts, both domestic and wild, in the Iquitos region, map the distribution of infected animals, and identify infecting leptospiral isolates to the serovar and molecular levels; and 3) Delineate the temporal and spatial relationship between anthropogenic environmental changes including deforestation, changes in land use patterns, and changes in mammalian faunal populations on the incidence of human leptospirosis cases. The data obtained from this project will provide insight into the potential of anthropogenic environment changes to alter the transmission of leptospirosis in the Peruvian Amazon. This multi-disciplinary, collaborative project involving Peruvian and U.S. investigators to study a disease of emerging importance in Peru utilizes a diverse set of disciplines (infectious disease epidemiology, mammalian ecology, public health, medical microbiology and molecular epidemiology , and the use of geographic information systems and remote sensing technologies) to answer ecological questions about leptospirosis with widespread general interest to many other fields.